The main goal of the proposed research is to establish what role tRNA synthetases and tRNA may have in cellular regulatory mechanisms. The main approach will be to analyze mutants defective in amino acyl tRNA synthetases. I am presently investigating mutants of E. coli with an altered tyrosyl-tRNA synthetase and will determine if the mutation has any effect on the ability of the cell to control the levels of the tyrosine biosynthetic enzymes. This study will include an extensive characterization of the properties of the purified mutationally-altered enzymes. I also propose to isolate tRNA synthetase mutants in animal cells. We will utilize amino acid analogues in the selection procedure.